8-120003003-G-T

Position:

• chr8-120003003-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_022783.4(DEPTOR):​c.817G>T​(p.Val273Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000696 in 1,436,536 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: DEPTOR NM_022783.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.61

Genes affected

DEPTOR (HGNC:22953): (DEP domain containing MTOR interacting protein) Involved in several processes, including negative regulation of TOR signaling; negative regulation of cell size; and negative regulation of protein kinase activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DEPTOR	NM_022783.4	c.817G>T	p.Val273Leu	missense_variant	6/9	ENST00000286234.6	NP_073620.2
DEPTOR	NM_001283012.2	c.514G>T	p.Val172Leu	missense_variant	4/7		NP_001269941.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DEPTOR	ENST00000286234.6	c.817G>T	p.Val273Leu	missense_variant	6/9	1	NM_022783.4	ENSP00000286234.5
DEPTOR	ENST00000523492.5	c.514G>T	p.Val172Leu	missense_variant	4/7	2		ENSP00000430457.1
DEPTOR	ENST00000518057.1	n.266G>T		non_coding_transcript_exon_variant	3/6	5

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 6.96e-7 AC: 1 AN: 1436536 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 712460

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.09e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 29

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 03, 2023

The c.817G>T (p.V273L) alteration is located in exon 6 (coding exon 6) of the DEPTOR gene. This alteration results from a G to T substitution at nucleotide position 817, causing the valine (V) at amino acid position 273 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.014	.;T
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.93	D;D
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.54	D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	.;M
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-1.2	N;N
REVEL	Benign	0.044
Sift	Benign	0.13	T;T
Sift4G	Uncertain	0.044	D;T
Polyphen		0.28	.;B
Vest4		0.56
MutPred		0.23		.;Loss of MoRF binding (P = 0.0992);
MVP		0.65
MPC		0.16
ClinPred		0.83	D
GERP RS		5.3
Varity_R		0.16
gMVP		0.36

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-121015242;